Dr Muhammad Jamaluddin
School of Biomedical Sciences and Pharmacy
- Phone:(02) 4921 7476
- PhD (Biochemistry), University of Queensland
- Medical Biochemistry
For publications that are currently unpublished or in-press, details are shown in italics.
Journal article (7 outputs)
Ko YA, Jamaluddin MFB, Adebayo M, Bajwa P, Scott RJ, Dharmarajan AM, et al., 'Extracellular matrix (ECM) activates Ã-catenin signaling in uterine fibroids', Reproduction, 155 61-71 (2018) [C1]
Â© 2018 Society for Reproduction and Fertility. Recent studies showed that genetic aberrations in the MED12 gene, probably through the canonical WNT/Ã-catenin pathway, lead to th... [more]
Â© 2018 Society for Reproduction and Fertility. Recent studies showed that genetic aberrations in the MED12 gene, probably through the canonical WNT/Ã-catenin pathway, lead to the pathogenesis of uterine fibroids. However, a comprehensive analysis of the WNT pathway in MED12-mutated and MED12-wildtype fibroids has not been performed. The objective of this study was to determine the status of the WNT pathway in human fibroids. We performed Sanger sequencing to define the MED12 mutational status of fibroids and normal myometrium samples. qPCR arrays were carried out to determine the status of the WNT signaling pathway in MED12-mutated and MED12-wild-type fibroids. Liquid chromatography-mass spectrometry (LC-MS), Western blotting and immunohistochemistry were used to monitor the expression of Ã-catenin. We showed that Ã-catenin expression was increased in fibroids compared to the adjacent myometrium samples. However, Ã-catenin expression showed no correlation with MED12 mutation status. Of all the WNT signaling components, WNT inhibitors showed the greatest differences in expression between fibroids and controls. WIF1, a WNT inhibitor, was identified as the most significantly upregulated gene in fibroids. We cultured primary fibroid cells on hydrogels of known stiffness to decipher the influence of biomechanical cues on Ã-catenin expression and revealed increased levels of Ã-catenin when cells were cultured on a stiffer surface. In conclusion, our data showed that Ã-catenin expression in fibroids occurs independently of MED12 mutations. Biomechanical changes upregulate Ã-catenin expression in fibroids, providing an attractive avenue for developing new treatments for this disease.
Jamaluddin MFB, Ko Y-A, Kumar M, Brown Y, Bajwa P, Nagendra PB, et al., 'Proteomic Profiling of Human Uterine Fibroids Reveals Upregulation of the Extracellular Matrix Protein Periostin.', Endocrinology, 159 1106-1118 (2018)
Jamaluddin MFB, Bailey UM, Schulz BL, 'Oligosaccharyltransferase subunits bind polypeptide substrate to locally enhance N-glycosylation', Molecular and Cellular Proteomics, 13 3286-3293 (2014)
Â© 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Oligosaccharyltransferase is a multiprotein complex that catalyzes asparagine-linked glycosylation of ... [more]
Â© 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Oligosaccharyltransferase is a multiprotein complex that catalyzes asparagine-linked glycosylation of diverse proteins. Using yeast genetics and glycoproteomics, we found that transient interactions between nascent polypeptide and Ost3p/Ost6p, homologous subunits of oligosaccharyltransferase, were able to modulate glycosylation efficiency in a site-specific manner in vivo. These interactions were driven by hydrophobic and electrostatic complementarity between amino acids in the peptidebinding groove of Ost3p/Ost6p and the sequestered stretch of substrate polypeptide. Based on this dependence, we used in vivo scanning mutagenesis and in vitro biochemistry to map the precise interactions that affect site-specific glycosylation efficiency. We conclude that transient binding of substrate polypeptide by Ost3p/Ost6p increases glycosylation efficiency at asparagines proximal and C-terminal to sequestered sequences. We detail a novel mode of interaction between translocating nascent polypeptide and oligosaccharyltransferase in which binding to Ost3p/Ost6p segregates a short flexible loop of glycosylation-competent polypeptide substrate that is delivered to the oligosaccharyltransferase active site for efficient modification.
Tan NY, Bailey UM, Jamaluddin MF, Mahmud SHB, Raman SC, Schulz BL, 'Sequence-based protein stabilization in the absence of glycosylation', Nature Communications, 5 (2014)
Asparagine-linked N-glycosylation is a common modification of proteins that promotes productive protein folding and increases protein stability. Although N-glycosylation is import... [more]
Asparagine-linked N-glycosylation is a common modification of proteins that promotes productive protein folding and increases protein stability. Although N-glycosylation is important for glycoprotein folding, the precise sites of glycosylation are often not conserved between protein homologues. Here we show that, in Saccharomyces cerevisiae, proteins upregulated during sporulation under nutrient deprivation have few N-glycosylation sequons and in their place tend to contain clusters of like-charged amino-acid residues. Incorporation of such sequences complements loss of in vivo protein function in the absence of glycosylation. Targeted point mutation to create such sequence stretches at glycosylation sequons in model glycoproteins increases in vitro protein stability and activity. A dependence on glycosylation for protein stability or activity can therefore be rescued with a small number of local point mutations, providing evolutionary flexibility in the precise location of N-glycans, allowing protein expression under nutrient-limiting conditions, and improving recombinant protein production. Â© 2014 Macmillan Publishers Limited. All rights reserved.
Mohd Yusuf SNH, Bailey UM, Tan NY, Jamaluddin MF, Schulz BL, 'Mixed disulfide formation in vitro between a glycoprotein substrate and yeast oligosaccharyltransferase subunits Ost3p and Ost6p', Biochemical and Biophysical Research Communications, 432 438-443 (2013)
Oligosaccharyltransferase (OTase) glycosylates selected asparagine residues in secreted and membrane proteins in eukaryotes, and asparagine (N)-glycosylation affects the folding, ... [more]
Oligosaccharyltransferase (OTase) glycosylates selected asparagine residues in secreted and membrane proteins in eukaryotes, and asparagine (N)-glycosylation affects the folding, stability and function of diverse glycoproteins. The range of acceptor protein substrates that are efficiently glycosylated depends on the action of several accessory subunits of OTase, including in yeast the homologous proteins Ost3p and Ost6p. A model of Ost3p and Ost6p function has been proposed in which their thioredoxin-like active site cysteines form transient mixed disulfide bonds with cysteines in substrate proteins to enhance the glycosylation of nearby asparagine residues. We tested aspects of this model with a series of in vitro assays. We developed a whole protein mixed disulfide interaction assay that showed that Ost6p could form mixed disulfide bonds with selected cysteines in pre-reduced yeast Gas1p, a model glycoprotein substrate of Ost3p and Ost6p. A complementary peptide affinity chromatography assay for mixed disulfide bond formation showed that Ost3p could also form mixed disulfide bonds with cysteines in selected reduced tryptic peptides from Gas1p. Together, these assays showed that the thioredoxin-like active sites of Ost3p and Ost6p could form transient mixed disulfide bonds with cysteines in a model substrate glycoprotein, consistent with the function of Ost3p and Ost6p in modulating N-glycosylation substrate selection by OTase in vivo. Â© 2013 Elsevier Inc.
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Conference (1 outputs)
Yi-An K, Jamaluddin M, Tanwar PS, 'Extracellular Matrix (ECM) and Wnt signalling nexus in human uterine leiomyomas', Perth (2017)
Grants and Funding
|Number of grants||2|
Click on a grant title below to expand the full details for that specific grant.
20181 grants / $17,307
Funding body: John Hunter Hospital Charitable Trust
20171 grants / $20,000
Funding body: John Hunter Hospital Charitable Trust